Kynurenine, decarboxylation

Pyridoxal phosphate is the coenzyme in a large number of amino acid reactions. At this point it is convenient to consider together 1,he mechanism of those pyridoxal-dependent reactions concerned with aromatic amino acids. The reactions concerned are (1) keto acid formation (e.g., from kynurenine, above), 2) decarboxylation (e.g., of 5-hydroxytrypto-phan to 5-hydroxytryptamine, p. 106), (3) scission of the side claain (e.g., 3-tyrosinase, p. 78 tryptophanase, p. 110 and kynureninase, above), and 4) synthesis (e.g., of tryptophan from indole and serine, p. 40). Many workers have considered the mechanism of one or more of these reactions (e.g., 24, 216, 361, 595), but a unified theory is primarily due to Snell and his colleagues (summarized in 593). Snell s experiments have been carried out largely in vitro, and it should be emphasized that in vivo it is the enzyme protein which probably directs the electromeric changes. 

Another interesting variant of tryptophan metabolism has been found in silkworm pupae (118), which form kynurine (4-hydroxyquinoline). This might arise by direct decarboxylation of kynurenic acid, but it is more likely (119) that it is formed by decarboxylation of kynurenine to kynuren-amine, which wmild be expected to give kynurine through the action of amino oxidase. 

Kynurenine formamidase catalyzes the hydrolysis of formylkynurenine. A variety of aromatic forma-mides will react, but the enzyme is more active with its natural than with the synthetic substrates. The product of the reaction, kynurenine, may then either be hydroxylated or decarboxylated. 

Kynurenic acid and xanthurenic acid, side products of the reaction, are the products of the transamination of the a-amino group of kynurenine and 3-hydroxy-kynurenine to a-ketoglutaric acid in the presence of pyridoxal phosphate and an enzyme found in mammalian liver and kidney, kynurenine transaminase. The keto acid resulting from the transamination reaction condenses spontaneously. Liver homogenate also decarboxylates 3-hydroxykynurenine to yield 4,8-de-hydroxyquinoline. Kynurenase may catalyze the cleavage of the side chain of kynurenine or 8-hydroxy-kynurenine and lead to the formation of alanine and... 

Kynurenine Metaholism. Kynurenine may be metabolized in five ways acetylation to iV -acetylkynurenine,i decarboxylation to kynuramine, oxidation to 3-hydroxykynurenine, cyclization to a quinoline derivative, and cleavage to yield anthranilic acid." The oxidation, cyclization, and cleavage reactions are components of major pathways of tryptophan metabolism. Ommochrome is composed of a series of heterocyclic condensed ring systems that have been shown to be derived from tryptophan via kynurenine. The individual steps in the enzymatic formation of the pigments have not separated. ... 

Functional end products of the essential amino acid tryptophan arise mainly through two distinctive pathways. The major pathway is degradation of tryptophan by oxidation, which fuels the kynurenine pathway (See 02011). The second and quantitatively minor pathway is hydroxylation of tryptophan and its subsequent decarboxylation to the indoleamine 5-hydroxytryptamine (serotonin) and subsequently melatonin. The metabolites of the kynurenine pathway, indicated as kynurenines, include quinolic acid and kynurenic acid. Quinolinic acid is an agonist of the NMDA receptor (see also section on glutamic acid), while kynurenic acid is a nonselective NMDA-receptor antagonist with a high affinity for the glycine site of the NMDA receptor (see also section on... 

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